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**mCTH-ANXA5** is an experimental tumor-targeted enzyme-prodrug fusion protein developed at the University of Oklahoma for recurrent metastatic ovarian cancer. It fuses annexin A5, which binds phosphatidylserine exposed on ovarian tumor cells and tumor-associated vasculature, to a mutant human cystathionine gamma-lyase containing E58N, R118L, and E338N substitutions. The engineered enzyme acquires methionine gamma-lyase-like activity and converts systemically administered selenomethionine into methylselenol at the tumor site, inducing reactive oxygen species-mediated cytotoxicity. In orthotopic murine ovarian-cancer models, mCTH-ANXA5 was evaluated with selenomethionine and, separately, in combination with anti-CD73 and anti-OX40 immunotherapies.
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